The long range goal of this proposal continues to be the mapping of human genes (functional loci) to specific chromosomes, regions of chromosomes and high resolution gene maps. The genes we have chosen to map play a significant role in human health and development. For this application, we have identified over 1,100 genes with sequences in databases that have not been mapped within the human genome. We will develop STSs from these sequences and map them to specific chromosomes and regions of chromosomes using our well-characterized and successful cell hybrid panels. After these gene markers have been mapped, primers will be sent to the MIT Center for Genome Research and the Iowa Cooperative Human Linkage Center for incorporation with their physical and gene linkage maps, respectively. An additional goal will be to continue mapping 75-100 human genes/year associated with disease and notable biological features that are requested by our collaborators. These genes will also be candidates for generating STSs from their sequences and incorporating them into the developing physical and linkage maps. The significance of this proposal is that (1) large numbers of human genes necessary for normal human biology will be mapped, (2) human gene sequences will be located in the genome at a specific site, (3) this number of mapped human genes will increase the resolution and completeness of the MIT and Iowa Center maps by about 10%, (4) these gene markers will add a significant biological feature to the developing physical and linkage maps that are being constructed with random genome markers, and (5) these additional mapped gene markers will help characterize, diagnose and predict genetic disease.